We report 14 patients (9 males, 5 females) aged 15-59 years, treated for malignant pheochromocytoma. These patients were observed during the 1966-1990 period along with 68 other patients presenting benign pheochromocytomas. From the initial general presentation of the 14 patients, two groups could be individualized. In seven patients, the initial presentation seemed benign. After the excision, the recovery was complete, but patients recurred on average 7.8 yr later (range 1-22 yr). Tumors were intraadrenal in six cases (5 single, 1 bilateral) and extraadrenal in one case. In the seven remaining patients, malignancy was evident from the first examination. The tumors were intraadrenal in 2 cases, extraadrenal in 5 cases. Frequency of extraadrenal locations (6/14) was in this series significantly higher than in benign forms (9/68). Diagnosis of malignancy was based on metastases in 12 cases (lymph nodes in 5, bones in 5, liver in 4, lung in 2, brain in 1) and on peritumoral extension in 2 cases. No biological specificity was detected in urinary excretion of catecholamines or its metabolites. In 6 patients so far studied, an uptake of 131I MIBG was found in the tumor and/or metastases. Four patients received therapeutic doses of 131I MIBG and in three of them, this treatment led to a good result within a follow-up range of 12 to 66 months.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the early and late effects of two types of ultra-long exercise on sympatho-adrenal and dopaminergic activity. With this aim both free and sulphoconjugated plasma catecholamines (CA), noradrenaline (NA), adrenaline (A), and dopamine (DA) were determined in two groups of athletes immediately after completion of 24-h running or a 10-h triathlon and on recovery during the next 1-3 days. Both races stimulated the sympathetic activity, but differences were observed in the CA pattern: the 24-h run induced a marked elevation of free and sulphoconjugated NA (+175% and +180%, respectively) but failed to alter significantly A and DA levels. The triathlon challenge increased the three conjugated CA (NA sulphate +350%; A sulphate +110%; DA sulphate +270%) and to a lesser extent free CA (NA +45%; A +30%). On the first post-exercise morning, a sustained intense noradrenergic activity was still present in the 24 h-runners, as evidenced by the large increase in free and sulphated NA levels (+140% and +100%, respectively). Such a prolonged activity was also indicated after completion of the triathlon, by the increase of NA sulphate (+140%) observed on the 1st recovery day. However, after the triathlon there was a decreased release of A from the adrenal medulla for several days. These data show that both types of ultralong exercise are able to induce for several hours a sustained sympathetic activation during the test and in the recovery period. Furthermore, the study shows that plasma conjugated CA may provide delayed and cumulative indexes of sympathetic activation, complementary to the instantaneous markers such as free CA.

The influence of long-term hypoxia on noradrenergic cell groups in the brain stem was assessed by estimating the changes in norepinephrine (NE) turnover in A1, A2 (subdivided into anterior and posterior parts), A5, and A6 groups in rats exposed to hypoxia (10% O2-90% N2) for 14 days. The NE turnover was decreased in A5 and A6 groups but failed to change significantly in A1. The NE turnover was increased in the posterior part of A2 and remained unaltered in the anterior part. In normoxic rats, the hypotensive drug dihydralazine induced a reverse effect, namely increased NE turnover in anterior A2 and no change in posterior A2. The neurochemical responses to hypoxia were abolished by transection of carotid sinus nerves. The results show that long-term hypoxia exerts differential effects on the noradrenergic cell groups located in the brain stem. Peripheral chemosensory inputs control the hypoxia-induced noradrenergic alterations. The A2 cell group displays a functional subdivision: the posterior part is influenced by peripheral chemosensory inputs, whereas the anterior part may be concerned with barosensitivity.

Cortical norepinephrine (NE) release and metabolism were studied by using chronic microdialysis in rats performing a treadmill exercise at 25 m/min with a 3% slope. Cortical microdialysates and peripheral blood were collected at rest, during 1- or 2-h treadmill running, and for 1 h after exercise. Microdialysate NE and its main metabolites, 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol, and plasma epinephrine (Epi) and NE were determined by high-performance liquid chromatography with electrochemical detection. The results show that treadmill running is able to stimulate concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e., NE turnover and release. The duration of the central activation and its prolongation over recovery period increases as the duration of the running increases. A positive correlation was found between the central noradrenergic activation and peripheral Epi secretion but not peripheral NE. These findings confirm and extend our previous observations in exercising men and give support to the hypothesis that the elevation of circulating Epi can be a relevant factor mediating, directly or indirectly, the exercise-induced central neurochemical, psychological, and cognitive changes.